) is a heterodimeric protein, first recovered from EBV-transformed B cell lines.It is a multifunctional cytokine, the properties of which bridge innate and adaptive immunity, acting as a key regulator of cell-mediated immune responses through the induction of T helper 1 differentiation. By promoting IFN-g production, proliferation, and cytolytic activity of natural killer and T cells, IL-12 induces cellular immunity. In addition, IL-12 induces an antiangiogenic program mediated by IFN-g^inducible genes and by lymphocyte-endothelial cell cross-talk. The immunomodulating and antiangiogenic functions of IL-12 have provided the rationale for exploiting this cytokine as an anticancer agent. In contrast with the significant antitumor and antimetastatic activity of IL-12, documented in several preclinical studies, clinical trials with IL-12, used as a single agent, or as a vaccine adjuvant, have shown limited efficacy in most instances. More effective application of this cytokine, and of newly identified IL-12 family members (IL-23 and IL-27), should be evaluated as therapeutic agents with considerable potential in cancer patients.Interleukin-12 (IL-12) is recognized as a master regulator of adaptive type 1, cell-mediated immunity, the critical pathway involved in protection against neoplasia and many viruses. This is supported by the analysis of numerous animal (1, 2) and human clinical studies that attribute improved clinical outcome (3) and mechanisms of IL-12 -based therapy (4) to strong type 1 responses in situ. Since the initial preclinical and clinical studies of IL-12, done over a decade ago, basic and translational science studies have contributed to the greater understanding of IL-12 immunobiology. In addition to its noted effects in the priming of T helper 1 (TH1) cell responses and IFN-g production by T and natural killer (NK) cells, more recent studies support its critical role as a third signal for CD8 + T cell differentiation (5, 6), and its ability to serve as an important factor in the reactivation and survival of memory CD4 + T cells (7). This is particularly relevant in the repolarization of CD4 + T cells from dysfunctional antitumor TH2 into TH1 cells in the cancer setting (8). Here, we review the immunomodulatory and antiangiogenic functions of IL-12, as well as the results of preclinical and clinical studies in which IL-12 was used as an anticancer agent.

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Lung cancer is the most common malignancy worldwide. Despite significant advances in diagnosis and treatment, mortality rates remain extremely high, close to incidence rates. Several targeted therapies have been recently introduced for the treatment of non-small cell lung cancer (NSCLC), the most common type of lung cancer. Nivolumab, a monoclonal antibody that targets programmed death-1 (PD-1), was the first immune checkpoint inhibitor approved for the treatment of patients with advanced/metastatic NSCLC not responding to platinum-based chemotherapy. Biomarkers predicting response to these therapies would allow early identification of non-responders and timely implementation of appropriate combination strategies, avoiding inadequate and expensive therapies. The role of the neutrophil to lymphocyte ratio and other blood cell count indexes as possible biomarkers of response has been recently investigated. We discuss the encouraging results reported on the topic, provide new data from our personal experience, and discuss opportunities for further research.

We report on experiences at the Software Sustainability Institute (SSI) in customizing and using the Trac system to provide a single platform for recording, managing and tracking a wide range of community interactions. We note the essential requirement of a lightweight, easy-to-use system for recording 'community metadata' and discuss the pros and cons of using Trac in this way for day-to-day operations within SSI, and more generally as a means to record and track interactions with a wide and potentially very large community.